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Baby β cells in danger
Susceptibility to type 1 diabetes involves genetic risk factors and potential environmental triggers, making it harder to predict which individuals will actually develop disease. Longitudinal samples collected starting shortly after birth from children at risk for type 1 diabetes were examined by Heninger et al. to scrutinize early immune responses. Some, but not all, of these children eventually developed autoimmunity; CD4+ T cells from those that progressed had a distinct phenotype after presentation of autoantigen, suggesting that they had already been somewhat activated, even before autoantibodies were detectable. These exciting findings indicate that cues that dictate type 1 diabetes development may be happening even earlier than expected, in infancy.
Abstract
Autoimmune diabetes is marked by sensitization to β cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in β cell antigen–responsive CD4+ T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of β cell antigen–responsive naïve CD4+ T cells from children who developed β cell autoimmunity was found in infancy, well before the appearance of β cell antigen–specific memory T cells or autoantibodies. The signature resembled a pre–T helper 1 (TH1)/TH17/T follicular helper cell response with expression of CCR6, IL21, TBX21, TNF, RORC, EGR2, TGFB1, and ICOS, in the absence of FOXP3, IL17, and other cytokines. The cells transitioned to an IFNG-TH1 memory phenotype with the emergence of autoantibodies. We suggest that the divergent naïve T cell response is a consequence of genetic or environmental priming during unfavorable perinatal exposures and that the signature will guide future efforts to detect and prevent β cell autoimmunity.
- Copyright © 2017, American Association for the Advancement of Science
